Identification of serum microRNAs as potential biomarkers in Pompe disease
Identification of serum microRNAs as potential biomarkers in Pompe disease
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DOI：
10.1002/acn3.50800
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发表时间：
2022-06-06
影响因子：
5.3
通讯作者：
Uson, Mercedes
中科院分区：
文献类型：
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作者：
Carrasco-Rozas, Ana;Fernandez-Simon, Esther;Uson, Mercedes
目的分析成人型庞贝氏症（AOPD）患者血清中microRNA的表达谱。方法采用microRNA PCR技术检测15例AOPD患者和5例正常对照血清中185种microRNA的表达。使用实时PCR在35名AOPD患者和10名对照中进一步研究了失调的microRNA的表达水平。此外，还研究了在血清样品中显示显著增加水平的骨骼肌microRNA表达。进行了microRNA血清水平与肌肉功能试验、肺活量测定和定量肌肉MRI之间的相关性（这些数据对应于ClinicalTrials.gov上的研究NCT 01914536）。结果我们鉴定了14种microRNA，与对照组相比，它们在AOPD患者血清样品中表现出不同的表达水平。我们在更大的患者队列中验证了这些结果，我们发现三种microRNA的水平增加，即所谓的dystromirs：miR-1- 3 p，miR-133 a-3 p和miR-206。这些microRNA参与肌肉再生，并且这些microRNA的表达在患者的肌肉活检中增加。microRNA水平与肌肉功能测试之间存在显著相关性。解释dystromirs的血清表达水平可能代表AOPD患者随访的额外生物标志物。
Objective To analyze the microRNA profile in serum of patients with Adult Onset Pompe disease (AOPD). Methods We analyzed the expression of 185 microRNAs in serum of 15 AOPD patients and five controls using microRNA PCR Panels. The expression levels of microRNAs that were deregulated were further studied in 35 AOPD patients and 10 controls using Real-Time PCR. Additionally, the skeletal muscle expression of microRNAs which showed significant increase levels in serum samples was also studied. Correlations between microRNA serum levels and muscle function test, spirometry, and quantitative muscle MRI were performed (these data correspond to the study NCT01914536 at ClinicalTrials.gov). Results We identified 14 microRNAs that showed different expression levels in serum samples of AOPD patients compared to controls. We validated these results in a larger cohort of patients and we found increased levels of three microRNAs, the so called dystromirs: miR-1-3p, miR-133a-3p, and miR-206. These microRNAs are involved in muscle regeneration and the expression of these was increased in patients' muscle biopsies. Significant correlations between microRNA levels and muscle function test were found. Interpretation Serum expression levels of dystromirs may represent additional biomarkers for the follow-up of AOPD patients.